Apical-driven cell sorting optimised for tissue geometry ensures robust patterning

Abstract

Tissue patterning coordinates morphogenesis, cell dynamics and fate specification. Understanding how these processes are coupled to achieve precision despite their inherent variability remains a challenge. Here, we investigate how salt-and-pepper epiblast and primitive endoderm (PrE) cells sort and robustly pattern the inner cell mass (ICM) of mammalian blastocysts. Quantifying cellular dynamics and mechanics together with simulations show a key role for the autonomously acquired apical polarity of mouse PrE cells in coupling cell fate and dynamics in tissue contexts. Specifically, apical polarity forms actin protrusions and is required for Rac1-dependent migration towards the ICM surface, where PrE cells are trapped due to decreased tension at their apical domain, while depositing an extracellular matrix gradient, breaking the tissue-level symmetry and collectively guiding their own migration. Tissue size perturbations and comparison with monkey blastocysts further demonstrate that the fixed proportion of PrE/epiblast cells is optimal and robust to variability in embryo size.

Self-organization of embryonic stem cells into a reproducible embryo model through epigenome editing

“…The results show that CRISPRa-induced cells display different patterns of angular movements over time when compared to non-induced sgGata6-mESCs and sgCdx2-mESCs, which was more pronounced for sgGata6-mESCs. The collective changes in movement distance and movement direction of induced sgGata6-mESCs is likely required for these cells to spatially organize themselves into ring-like structures during tissue morphogenesis (Figure 3F, Supplemental Figure 3) [45].…”

“…The results show that CRISPRa-induced cells display different patterns of angular movements over time when compared to non-induced sgGata6-mESCs and sgCdx2-mESCs, which was more pronounced for sgGata6-mESCs. The collective changes in movement distance and movement direction of induced sgGata6-mESCs is likely required for these cells to spatially organize themselves into ring-like structures during tissue morphogenesis ( Figure 3F, Supplemental Figure 3 ) [45]. Together, our single-cell live imaging shows that intrinsic induction of fate in a few randomly positioned cells is sufficient to generate orchestrated cellular motion and growth behavior that results in formation of spatial patterns, suggesting a mostly underappreciated, yet important, role for dynamic cellular movement during mammalian embryonic pattern formation.…”

A novel ground truth dataset enables robust 3D nuclear instance segmentation in early mouse embryos

“…Interestingly, a subset of ICM nuclei experienced an increase in aspect ratio during the last 3-4 hours of the time-lapse (see S10 Fig(C’,D’)). This latter subset may correspond to primitive endoderm nuclei that flatten as the primitive endoderm forms a monolayer (Fig 1(B)) [35].…”

“…Additionally, although TE nuclei tended to have higher aspect ratios than ICM nuclei, the distributions significantly overlapped, and both the median TE and ICM nuclear aspect ratios increased by the >100-cell stage (S10 Fig) . Interestingly, a subset of ICM nuclei experienced an increase in aspect ratio during the last 3-4 hours of the time-lapse (see S10 Fig( C',D')). This latter subset may correspond to primitive endoderm nuclei that flatten as the primitive endoderm forms a monolayer (Fig 1 (B)) [35].…”